Hydrogen peroxide mediates cadmium accumulation in the root of a high cadmium-accumulating rice (Oryza sativa L.) line.

Hydrogen peroxide (H2O2) is a vital signaling molecule in response to cadmium (Cd) stress in plants. However, the role of H2O2 on Cd accumulation in root of different Cd-accumulating rice lines remains unclear. Exogenous H2O2 and 4-hydroxy-TEMPO (H2O2 scavenger) were applied to investigate the physiological and molecular mechanisms of H2O2 on Cd accumulation in the root of a high Cd-accumulating rice line Lu527-8 through hydroponic experiments. Interestingly, it was found Cd concentration in the root of Lu527-8 increased significantly when exposed to exogenous H2O2, while reduced significantly when exposed to 4-hydroxy-TEMPO under Cd stress, proving the role of H2O2 in regulating Cd accumulation in Lu527-8. Lu527-8 showed more Cd and H2O2 accumulation in the roots, along with more Cd accumulation in cell wall and soluble fraction, than the normal rice line Lu527-4. In particular, more pectin accumulation, especially low demethylated pectin, was observed in the root of Lu527-8 when exposed to exogenous H2O2 under Cd stress, resulting in more negative functional groups with greater capacity to binding Cd in the root cell wall of Lu527-8. It indicated that H2O2-induced cell wall modification and vacuolar compartmentalization contributes greatly to more Cd accumulation in the root of the high Cd-accumulating rice line.

Cell Therapy With G-CSF-Mobilized Stem Cells in a Rat Osteoarthritis Model.

G-CSF-mobilized peripheral blood stem cells (gm-PBSCs) offer a convenient cell source for treatment of hematopoietic and vascular disorders. Whether gm-PBSCs provide beneficial effects on skeleton diseases, such as osteoarthritis (OA), remains unknown. This study was undertaken to address the hypothesis that gm-PBSCs promote articular regeneration in OA. Here we studied the effect of single-dose intra-articular injection of gm-PBSCs from male donors delivered in hyaluronic acid (HA) on papain-induced OA in the knee joints of female Sprague-Dawley (SD) rats. Contralateral OA knee joints received single-dose HA alone and served as vehicle controls. We evaluated the histologic changes in glycosaminoglycan, type II collagen, type X collagen, modified Mankin score, and cell apoptosis rate in the articular cartilage of rat knees. We demonstrated that gm-PBSCs were mobilized to the peripheral blood via G-CSF infusion for 5 days in SD rats with increasing CD34(+) percentage up to 55-fold. We showed that gm-PBSCs inhibit progression of papain-induced OA via reducing articular surface irregularity, fibrillation, and erosion, preventing cellular necrosis and loss of chondrogenic proteins, such as glycosaminoglycan and type II collagen, at both 3 and 6 weeks after treatment. Moreover, gm-PBSCs reduced modified Mankin scores and cellular apoptosis rates compared with HA alone. Our findings demonstrate that HA plus gm-PBSCs, rather than HA alone, inhibits progression of OA in rats in vivo. Thus, intra-articular injection of gm-PBSCs is a convenient protocol for treating OA with consistent beneficial effects.

Tumor-derived tumor necrosis factor-alpha promotes progression and epithelial-mesenchymal transition in renal cell carcinoma cells.

Pro-inflammatory cytokines and chemokines are involved in promoting tumorigenesis by facilitating tumor proliferation and metastasis. The serum levels of interleukin (IL)-6, IL-1 beta, and tumor necrosis factor-alpha (TNF-alpha) are significantly elevated in patients with renal cell carcinoma (RCC). However, the mechanisms of how these cytokines participate in the progression of RCC remains unknown. In the present study, we investigated the effects of tumor-derived cytokines on invasion and the epithelial-mesenchymal transition (EMT) of RCC cells. We found that expression of IL-1 beta, IL-6, TNF-alpha, hypoxia-inducible factor-alpha (HIF-1 alpha), and matrix metalloproteinase-2 (MMP2) were significantly elevated in high malignancy A498 cells compared to low malignancy 786-O cells. The invasion ability of A498 was three-fold higher than that of 786-O cells. The invasiveness of 786-O cells was markedly enhanced by adding conditioned medium derived from A498 cells. This phenomenon was significantly inhibited by immunodepletion of TNF-alpha followed by MMP2, IL-6, or IL-1 beta from A498 conditioned medium. Synergistic inhibition was also noted after simultaneous immunodepletion of TNF-alpha, IL-1 beta, and IL-6. RCC cell lines with higher malignancy produced more TNF-alpha, which was correlated with their stronger invasive ability. The invasiveness of 786-O cells was significantly promoted by TNF-alpha in a dose-dependent manner. Moreover, TNF-alpha induced the EMT of 786-O cells by repressing E-cadherin, promoting vimentin expression, and activating MMP9 activity. Our findings demonstrate that pro-inflammatory cytokines, especially TNF-alpha, can enhance invasion and the EMT of renal cancer cells, which provides a therapeutic target to prevent and treat advanced RCC.